Homoharringtonine Compared With Hydroxyurea for Chronic Myelogenous Leukemia That Has Not Responded to Interferon Alfa

This study has been terminated.
(Poor accrual)
Sponsor:
Collaborators:
Southwest Oncology Group
Information provided by:
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
NCT00004933
First received: March 7, 2000
Last updated: August 1, 2011
Last verified: August 2011
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known if homoharringtonine is more effective than hydroxyurea for chronic myelogenous leukemia that has not responded to interferon alfa.

PURPOSE: Randomized phase III trial to compare the effectiveness of homoharringtonine with that of hydroxyurea in treating patients who have chronic myelogenous leukemia that has not responded to interferon alfa.


Condition Intervention Phase
Leukemia
Drug: hydroxyurea
Drug: Homoharringtonine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Study of Interferon-Refractory Patients With BCR/ABL(+) Chronic Myelogenous Leukemia (CML) Treated With Homoharringtonine (NSC #141633) vs. Hydroxyurea

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: January 2000
Primary Completion Date: May 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Homoharringtonine Drug: Homoharringtonine
2.5 mg/ sq m/ day CIVI for 14 days
Active Comparator: Hydroxyurea Drug: hydroxyurea
0.5 to 5 grams PO per day

Detailed Description:

OBJECTIVES: I. Compare the overall survival of interferon alfa refractory chronic myelogenous leukemia patients treated with homoharringtonine to those treated with hydroxyurea. II. Compare the time to progression of these patients treated with these two drugs. III. Estimate the complete and major cytogenetic response and describe the serial cytogenetics of these patients treated with these two drugs.

OUTLINE: This is a randomized study. Patients are randomized to receive one of two treatments. Arm I: Induction: Patients receive homoharringtonine IV continuously over 24 hours daily for 14 days. Induction continues every 28 days for a maximum of 6 courses or until hematopoietic recovery. Maintenance: Patients receive homoharringtonine IV continuously over 24 hours daily for 5 days. Treatment repeats every 28 days. Arm II: Induction: Patients receive oral hydroxyurea daily for 28 days until acceptable blood counts are achieved. Maintenance: Patients receive oral hydroxyurea daily every 28 days to maintain acceptable blood counts. Treatment in both arms continues for a minimum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for a maximum of 10 years.

PROJECTED ACCRUAL: A total of 480 patients (240 per arm) will be accrued for this study within 4 years.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS: Cytologically proven chronic phase chronic myelogenous leukemia Philadelphia chromosome detectable by cytogenetic studies OR 1 of the following: BCR/ABL protein detectable by immunoblotting BCR/ABL rearrangement detectable by Southern blot analysis Polymerase chain reaction positive fusion transcripts for BCR/ABL BCR/ABL translocation present by fluorescence in situ hybridization No prior intolerance or failure to respond to hydroxyurea Must have failed adequate trial (5M units/m2/day) of interferon alfa (IFN) or the combination of IFN and cytarabine as defined by 1 of the following: Failure to achieve complete hematologic response after 6 months of IFN Failure to achieve any cytogenetic response (i.e., still 100% Philadelphia chromosome positive) after 12 months of IFN Intolerable adverse effects of IFN after at least 1 month of IFN Significant documented toxicity of grade 3 or greater due to IFN required Loss of a prior hematologic remission or cytogenetic response to IFN Two-fold increase in WBC count compared to WBC count when IFN initiated

PATIENT CHARACTERISTICS: Age: 16 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified Cardiovascular: No uncontrolled tachyarrhythmias (e.g., atrial fibrillation, paroxysmal superventricular tachycardia, or ventricular tachycardias not adequately controlled) Other: Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 7 days since prior interferon alfa Chemotherapy: See Disease Characteristics No prior homoharringtonine Less than 180 days cumulative prior hydroxyurea No more than 60 days hydroxyurea after failing interferon Endocrine therapy: No concurrent hormones except for nondisease related conditions (e.g., insulin for diabetes, estrogen for osteopenia) Concurrent steroids for adrenal failure allowed Radiotherapy: No concurrent palliative radiotherapy Surgery: No concurrent splenectomy except for emergency management

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004933

  Show 133 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Southwest Oncology Group
Investigators
Study Chair: Meir Wetzler, MD Roswell Park Cancer Institute
Study Chair: Harry P. Erba, MD, PhD University of Michigan Cancer Center
  More Information

No publications provided

Responsible Party: Monica M Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00004933     History of Changes
Other Study ID Numbers: CDR0000067617, U10CA031946, CLB-19807, SWOG-C19807
Study First Received: March 7, 2000
Last Updated: August 1, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Cancer and Leukemia Group B:
relapsing chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
Philadelphia chromosome positive chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Homoharringtonine
Hydroxyurea
Interferons
Harringtonines
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antisickling Agents
Hematologic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 22, 2014